title: The making of I-BET762, a BET bromodomain inhibitor now in clinical development.
abstract: Bromodomain and extra-terminal (BET) proteins belong to a class of proteins collectively called epigenetic "readers". BET bromodomains have emerged as promising drug targets for treatment of cancers, inflammatory diseases, and other medical conditions. GlaxoSmithKline scientists have successfully optimized a class of benzodiazepines as inhibitors of BET bromodomains, without any prior knowledge of identified molecular targets. It thus is possible to hit a target without aiming at it. The optimized lead compound I-BET762 is currently being evaluated in a phase I clinical trial for treatment of human cancer.
authors.affiliation: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chao-Yie
authors.initials: CY
authors.lastname: Yang
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D000092468:Bromodomain Containing Proteins
chemical_list: D000970:Antineoplastic Agents; D001569:Benzodiazepines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C554645:molibresib